1. Field of the Invention
The invention relates to a method of producing a filled plastic syringe body for medical purposes. Such a syringe body consists of a syringe cylinder having two ends, an outlet end and a rear end. A plunger stopper is inserted into the rear end, thereby sealing it. The outlet end is provided with an integrally molded head designed to accommodate an application element. The head is sealed by means of a removable sealing element for storage.
Such a syringe body may be, for example, a syringe body for a filled plastic disposable syringe, also known as a ready-to-use syringe, such as those whose dimensions are defined in the standards DIN 13,098 for unfilled plastic disposable syringes and in DIN ISO 11,040, part 4, for prefilled glass syringes. The syringe body for these ready-to-use syringes consists of a syringe cylinder having a finger rest on the end that is sealed with the plunger stopper and a syringe head on its outlet end.
Such a syringe body may also be a syringe cylinder, which is similar to the syringe body for a finished, ready-to-use syringe, but without the finger rest. Such a syringe cylinder is referred to below as a syringe ampule.
Such a syringe body may also be a cartridge ampule such as those whose configuration is stipulated in the standards DIN ISO 11,040, parts 1-3, and DIN ISO 13,926-1 for cartridge ampules with glass cylinders. As indicated by these standards, the cartridge ampules generally belong to the "pre-filled syringe" category. They consist of a syringe cylinder, the cartridge ampule cylinder, having an integrally molded neck part on the outlet end with a flat mouth edge and an edge bead. The outlet end can be sealed tightly by a flanged aluminum cap and a washer. The other end of the cylinder can be sealed with a plunger stopper.
2. Background of the Related Art
Ready-to-use plastic syringes of the above-mentioned type, especially small-volume ready-to-use syringes with a volume preferably in the range of 1-10 mL, are usually manufactured by producing the syringe body in a production plant that processes plastics into pharmaceutical packages. The resulting syringe bodies, after intermediate storage, are then shipped to a pharmaceutical plant where they are filled and sealed tightly, ready for use.
Production of such a syringe body is disclosed, for example, by World Patent WO 95/12482 and by German Patent DE 4,438,360 A1. According to these references, the syringe body is first produced by injection molding, at least under clean room (low particle count) conditions, its inside wall is optionally siliconized, and the syringe head is sealed by a sealing cap, referred to as a tip-cap, which is made of a rubbery material. As a rule, the syringe body produced in this way is packaged hermetically in a low-particulate and bacteria-proof container at the end of the manufacturing process. The syringe body then undergoes a sterilization process, which is usually performed at another company. Gamma rays can be used for sterilization. The body is then ready for intermediate storage or for shipping to the filling plant. The filling and sealing operation at the pharmaceutical company of the ready-to-use syringe is described, for example, in the article by H. Dollinger, "Filling disposable syringes in a high-performance compact system," published in the journal Die Pharmazeutische Industrie [The Pharmaceutical Industry], vol. 56, no. 1 (1994), which describes the filling of ready-to-use glass syringes. Typical process steps include removal of the as-delivered syringe body, optional cleaning, drying and sterilizing, if the syringe body was not sterilized on delivery, filling and sealing the syringe body, in most cases in combination with sterilization of the filled syringe body, and labeling and further finishing for shipping to the consumer. The production and filling of plastic syringe ampules and plastic carpules are similar.
The above-mentioned interfaces between the manufacturer of the plastic packaging material (plastics processing plant), the plant which performs the sterilization of the empty packaging material and the filling pharmaceutical plant is disadvantageous for a variety of reasons. The main reasons are the additional required steps of shipping, packaging and unpackaging of the syringe elements, separation, quality assurance and the additional risks of microbiological and particulate contamination in storage and shipping of the unfilled syringe cylinders for the respective type of syringe body. For example, the syringe body could develop a static charge during shipping that could result in dust adhering to the body which would have to be removed before filling.
Furthermore, there is a considerable interface-related expense associated with cleaning, drying and sterilization. This expense is very high with a glass syringe body according to the related art cited above, although glass bodies (in contrast with plastic bodies) can still be dried relatively easily by using high temperatures. With plastic bodies, it is even more expensive. These expensive procedures are described, for example, in European Patent EP 227,401, which also defines a special washing process. Furthermore, for injection molding of syringe bodies, an internal core is necessary which results in intimate contact with the hot polymer melt and a friction process on the complete inside surface in extracting the core. This in turn creates abrasion particles and thus necessitates the expensive washing and depyrogenization methods described in the above-mentioned European patent.
It is also known in the packaging industry that the packaging body can be manufactured and also filled and sealed, ready for use, in a single closed manufacturing line, i.e., a line automated for one pass operation, under controlled ambient conditions.
One such method, which has become known by the term "blow-fill-seal," is described, for example, in U.S. Pat. Nos. 3,919,374, 4,671,763 and 4,995,511. In this method, heat-softened plastic granules are injected into a mold by extrusion blow molding. A pharmaceutical packaging body is produced thereby which is filled while still in the mold and then sealed tightly.
However, this blow molding method allows only low-temperature processing of soft plastic materials such as polypropylene and polyethylene. It is possible to manufacture only containers whose inside dimensions permit relatively large tolerances because a core that predetermines the inside dimension with a narrow tolerance cannot be used in the blow molding method. Thus, bottle-like containers which are filled and sealed immediately after unmolding, i.e., while still hot, are typically produced with the known blow molding method. The inside dimensions of such containers are subject to relatively large tolerances, although they are not critical for the functionality of the container.
Primary pharmaceutical packaging materials such as filled plastic syringes or vials cannot be manufactured by this known blow molding method because this type of pharmaceutical packaging requires a nondeformable plastic material and low tolerances in the inside container diameter to guarantee an adequate seal during storage of the filled syringes and vials. Such syringes and vials are typically stored for a year or more.
Thus, it is an object of the invention to control the method for producing a filled plastic syringe body in such a way that it can be carried out easily, while minimizing the logistics costs and improving the siliconization of the plastic syringe body.